Economic Burden of Reported Lyme Disease in High-Incidence Areas, United States, 2014–2016

Approximately 476,000 cases of Lyme disease are diagnosed in the United States annually, yet comprehensive economic evaluations are lacking. In a prospective study among reported cases in Lyme disease–endemic states, we estimated the total patient cost and total societal cost of the disease. In addition, we evaluated disease and demographic factors associated with total societal cost. Participants had a mean patient cost of ≈$1,200 (median $240) and a mean societal cost of ≈$2,000 (median $700). Patients with confirmed disseminated disease or probable disease had approximately double the societal cost of those with confirmed localized disease. The annual, aggregate cost of diagnosed Lyme disease could be $345–968 million (2016 US dollars) to US society. Our findings emphasize the importance of effective prevention and early diagnosis to reduce illness and associated costs. These results can be used in cost-effectiveness analyses of current and future prevention methods, such as a vaccine.


Perspective) and Societal Medical Costs (Societal Perspective)
To estimate the total patient cost, we summed self-reported medical costs, nonmedical costs, cost of productivity losses, and other related costs over all surveys. For nonmedical costs related to travel for clinician, pharmacy, or laboratory visits, the self-reported roundtrip mileage per visit was multiplied by the standard mileage rate from the Internal Revenue Service for the respective year (1). To calculate cost estimates for productivity losses, self-reported hours missed from work for adult participants or parents of pediatric participants were multiplied by the hourly earnings by age and sex derived from Grosse et al. (2), which uses the human capital approach to estimate annual market and non-market productivity from the US Census Bureau's American Community Survey and American Time Use Survey.
We calculated the societal medical cost per participant (regardless of who pays) by summing the mean cost per CPT code collected for each participant. The codes represented clinician visits, consultation and related in-office procedures, diagnostic testing, therapy, hospitalization, emergency department (ED) visits, or other procedures or relevant costs. Mean cost for each CPT code collected for participants with private insurance was extracted from IBM MarketScan Research Databases, which include national medical claims data for privately insured persons up to age 65 and their dependents. Costs for CPT codes collected for nonprivately insured participants were extracted from the Physician Fee Schedule National Payment Amount File from the Centers for Medicare and Medicaid Services (CMS) (3). Both MarketScan and CMS costs reflect reimbursements made for charges for medical procedures and services and include the amount paid by the insurer as well as the beneficiary (such as deductibles, copays, and coinsurance). We did not collect billing codes from pharmacies or laboratories. Therefore, we extracted the mean cost of the recommended antibiotics for Lyme disease (LD) by state and study year from MarketScan drug cost data and added this cost to each participant's total societal medical cost (4)(5)(6)(7)(8). Because laboratory evidence of infection is required to meet criteria for confirmed disseminated or probable disease (9), we added the cost of the recommended twotiered LD diagnostic testing to the total societal medical cost for all participants in these disease categories who did not already have these CPT codes documented. We excluded from analysis participants for whom CPT code collection was incomplete due to provider nonresponse to code collection requests. We also excluded individual CPT codes deemed unrelated to LD, per consultation with an infectious disease physician, that were collected coincidentally from providers (Appendix Table 5).

Equation 1. Multivariable Linear Regression Model Equation
We used a multivariable linear regression model to estimate the relative impact of our independent variables of interest on the total societal cost of LD per participant. As is typical for healthcare cost data, the distribution of total cost was highly skewed, resulting in heteroskedasticity of the residuals in the model (10). Therefore, we transformed total societal cost per participant using natural logarithms and conducted sampling-weighted least squares regression. The basic equation is as follows: log(yi) = β0 + βixi + εi where Yi, is the dependent variable, the total societal cost of LD for patient i; Xi is a vector of covariates; and εi is a mean-zero random error. The equation is written as follows for our specific vector of covariates (i.e., independent variables of interest and potential confounders): log(yi) = β0 + β1Disease category + β2Age group + β3Sex + β4State + β5Insurance status + β6Income + β7Study year + εi Baseline costs came from the intercept term, β0, which represents a patient with confirmed localized Lyme disease, female, aged <18 years, with residence in CT, without private insurance, with income <$60,000, and study year of 2014. Resulting β coefficients were back transformed by exponentiation, interpreted as the multiplicative difference in the geometric mean of the total cost of Lyme disease for a 1-unit difference in the independent variable of interest after adjusting for confounders. For interpretability, we calculated the percent difference in cost from baseline for each level of each independent variable, excluding reference (i.e., baseline) levels (Percent difference = (Exp(coefficient) -1) * 100). These additional costs were added or subtracted to the baseline costs for each independent variable of interest (Table 6, LINK; Appendix Table 8).

Per Participant to Annual, Aggregate Total LD Cost to U.S. Society
Previous research has demonstrated that LD surveillance case numbers are likely 8-12fold underreported (11,12), with a recent study estimating 476,000 diagnosed cases per year (13).
The table below shows total cases by confirmed localized, confirmed disseminated, and probable disease per the proportions found in surveillance data. Case numbers by disease category are multiplied by the mean and median total cost per participant estimated from this study to get the aggregate cost per disease category (Appendix Table 9). When summed, the mean total cost of LD in the U.S. annually is approximately $968,444,834, while the median is $345,164,936 (2016 USD, Appendix Table 10). In 2020 USD, the mean cost is $1,039,260,297 using the Consumer Price Index (CPI) for all consumers and $1,078,657,584 when using the CPI for medical care (14), with median costs at $370,404,385 and $384,446,034, respectively (Appendix Table 10).   Injection, acyclovir, 5 mg 1 824 *An infectious disease physician with subject matter expertise in Lyme disease deemed these CPT codes to be unrelated to Lyme disease; 54 instances with these 30 codes recorded were deleted from the dataset before all analyses.